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Hormone-associated meningiomas tend to stop growing or decrease in size after cessation of certain progestins, mainly cyproterone acetate. We report three observations on the natural history of hormone-associated intraosseous meningiomas, showing in a first patient that those tumors may grow rapidly under nomegestrol. We then demonstrate the sustained growth of intraosseous hormone-associated meningiomas after cessation of promesgestone and nomegestrol, independently of the intracranial portion, which concurrently decreased in size in the second case or was resected at the time of nomegestrol withdrawal in the third case, thus giving new insights into the tumorigenesis mechanisms of hormone-associated intraosseous meningiomas.

Purpose Middle meningeal artery (MMA) embolization is emerging as a potential treatment of chronic subdural hematomas (CSDHs). The purpose of this study is to describe MMA angiographic anatomy in relation to CSDH embolization. Methods This retrospective monocentric study was performed on imaging data of MMA embolization procedures for CSDH treatment performed between March 15, 2018 and April 30, 2020. Imaging data, including digital subtraction angiography (DSA) were reviewed independently by two physicians. Discrepancies were resolved by consensus. The MMA bifurcation pattern was analyzed according to an extended Adachi classification. Relations of the MMA with the ophthalmic artery (OA) were also analyzed. Results In this study, 140 MMAs were analyzed. Dominance of the anterior branch (type I) was observed in only 57/140 (41%) MMAs with a moderate interobserver agreement for classifying MMA into type I against all other (κ = 0.53, 95% confidence interval, CI 0.39–0.67). The posterior branch presented a proximal origin (type A), at the point of emergence of the MMA from the foramen spinosum or its immediate vicinity, in 48/135 (36%) MMAs with a very good interobserver agreement for classifying MMAs into type A against all other (κ = 0.82, 95% CI 0.72–0.92). An angiographic relationship with the OA was observed in 26 MMAs (19%). Conclusion In the majority of CSDH patients both anterior and posterior branches of the MMA should be targeted to achieve extensive convexity devascularization. Frequent anatomical variations of the MMA with respect to emergence of the posterior branch and MMA orbital branches are expected to impact CSDH embolization strategy.

BackgroundThere is no universal management protocol concerning invasive malignant tumors of the scalp with bone and dura mater invasion. The aims of this study were to report and discuss our experience in the management of these forms of tumors.MethodsWe retrospectively reviewed all consecutive patients of microsurgical scalp reconstruction performed after resection of invasive cutaneous malignancies of the scalp, calvarium, and dura mater from 2017 to 2019, at Pitié-Salpêtrière University Hospital (Paris, France).ResultsFive patients met inclusion criteria. There were three squamous cell carcinomas and two sarcomas. Mean age at surgery was 63.6 years. The sex ratio male/female was 4. Two received radiation prior to resection and two patients had a history of prior scalp tumor surgery. All the patients underwent craniectomy and the mean cranial defect size was 41 cm2. Cranioplasty was performed in one patient. Soft tissue coverage was provided by free tissue transfer of latissimus dorsi muscle in all patients. In four patients, split thickness skin graft was performed in a second surgical stage few weeks later. There were no intraoperative complications and no complications into the donor site for the tissue transfer or the skin graft. Two patients had flap necrosis that healed after a new free flap of latissimus dorsi.ConclusionsWide resection with craniectomy and reconstruction with microvascular free tissue transfer provides safe and reliable treatment of recalcitrant invasive scalp skin cancers. The surgical management of these complex patients is a challenge that must be conducted by trained, experienced, and multidisciplinary teams.

Although their intention was to create a model of meningioma, investigators instead observed the development of cerebral cavernous malformations in their engineered mice, prompting them to test the implicated genes in patients with these malformations.

Purpose This study aimed to assess the benefit-risk ratio by determining diagnostic yield and safety of brainstem biopsies in adult patients. The secondary objectives were (i) to compare brainstem biopsy safety and postbiopsy patients’ outcomes and survival with those of patients biopsied for a brain or cerebellar lesion, and (ii) to assess the impact of brainstem biopsy on final diagnosis and further therapeutic management. Methods Among 1784 stereotactic biopsies performed in adult patients at a tertiary center between April 2009 and October 2020, we retrospectively examined 50 consecutive brainstem biopsies. We compared variables regarding diagnostic yield, safety and post-biopsy outcomes between brainstem biopsy patients and brain/cerebellum biopsy patients. Results Brainstem biopsy led to a diagnosis in 86% of patients (94.6% in patients with suspected tumor). Lesion contrast enhancement on imaging was the sole predictor of obtaining a diagnosis. Rates of symptomatic complications and mortality were significantly higher in brainstem biopsy patients compared to brain/cerebellum biopsy patients (20% vs 0%; p  < 0.001 and 6% vs 0%; p  = 0.01, respectively). Transfrontal trajectory and prebiopsy swallowing disorders were predictors of brainstem biopsy-related symptomatic complications. Brainstem biopsy findings led to diagnostic change in 22% of patients. Conclusions Stereotactic biopsy in adult patients with brainstem lesion has a high diagnostic yield. Although stereotactic brainstem biopsy is associated with more functional and fatal complications than biopsies targeting the brain/cerebellum, its safety profile appears acceptable. Thus, the benefit-risk ratio of stereotactic biopsy in patients with brainstem lesion is favorable but should nevertheless be carefully weighted on a case-by-case basis.

PurposeGrade 3 meningiomas, although rare, are associated with high morbidity and mortality. The respective impacts of extent of surgical resection and adjuvant radiotherapy are still debated. Moreover, anaplastic meningiomas are studied in heterogenous cohort of de novo and progressive anaplastic tumors.MethodsWe conducted a retrospective multicentric study on patients operated from a de novo anaplastic meningioma between 1999 and 2021. A centralized pathological review using 2016 WHO criteria was performed for all cases. Patients with history of radiotherapy or NF2-related Schwannomatosis were excluded.ResultsSixty-five patients were included in the study. Median progression free survival was 23 months and median overall survival was 2 years. Neither quality of resection nor adjuvant radiotherapy alone were predictive of better overall survival. Progression free survival were impacted by combination of gross-total resection and adjuvant radiotherapy (HR = 0.47 CI95% = [0.24–0.92], p = 0.027) and age at diagnosis (HR = 2.92 CI95% = [1.38–6.21], p = 0.005) in univariate analyses. Within anaplastic tumors, those graded on mitosis number had a poorer prognosis than those graded on overt anaplasia. Among anaplastic tumors with high mitotic score (> 20/10HPF), progression free survival were impacted by postoperative radiotherapy (HR = 0.44 CI95% = [0.22–0.88], p = 0.020) and gross total resection and adjuvant radiotherapy association (HR = 0.44 CI95% = [0.21–0.90], p = 0.024) in univariate analyses.ConclusionSimpson grade didn’t show any impact on overall survival. Gross total resection + adjuvant radiotherapy favorably impacted progression free survival in our cohort of de novo anaplastic meningiomas.

Despite their rarity, PIK3CA mutations in meningiomas have raised interest as potentially targetable, ubiquitous mutations owing to their presence in sporadic benign and malignant tumors but also in hormone-related cases. Using new genetically engineered mouse models, we here demonstrate that Pik3ca mutations in postnatal meningeal cells are sufficient to promote meningioma formation but also tumor progression in mice. Conversely, hormone impregnation, whether alone or in association with Pik3ca and Nf2 mutations, fails to induce meningioma tumorigenesis while promoting breast tumor formation. We then confirm in vitro the effect of Pik3ca mutations but not hormone impregnation on the proliferation of primary cultures of mouse meningeal cells. Finally, we show by exome analysis of breast tumors and meninges that hormone impregnation promotes breast tumor formation without additional somatic oncogenic mutation but is associated with an increased mutational burden on Pik3ca-mutant background. Taken together, these results tend to suggest a prominent role of Pik3ca mutations over hormone impregnation in meningioma tumorigenesis, the exact effect of the latter is still to be discovered.

Tumor-associated macrophages and microglia (TAMs) are highly abundant myeloid cells in gliomas, with their phenotypes and immune responses shaped by ontogeny and microenvironment. TAMs display distinctive transcriptional programs based on the IDH status of tumors, yet the underlying signaling mechanisms remain largely unknown. Herein, we uncover that CD11B+ myeloid cells in human IDH-mutant gliomas exhibit DNA hypermethylation, predominantly at distal enhancers. This hypermethylation impairs the binding of core transcription factors that govern microglial responses, resulting in reduced expression of inflammatory and glycolytic metabolism programs. Prolonged exposure of human primary microglia to D-2-hydroxyglutarate (D-2HG) inhibits TET-mediated demethylation at lineage-specific enhancers, evidenced by elevated 5mC/5hmC ratios near binding motifs. D-2HG-treated microglia showed reduced proinflammatory capacity and enhanced oxidative phosphorylation, consistent with the remodeled enhancer landscape. Conversely, depletion of D-2HG following treatment of a glioma patient with an IDH-mutant inhibitor unleashed microglial reactivity, as assessed by snRNA-seq. Our findings provide a mechanistic rationale for the hyporesponsive state of microglia in IDH-mutant gliomas and support the concept that oncometabolites may disrupt the function of immune cells residing in the tumor microenvironment.Competing Interest StatementL.A.S. is a scientific advisor and co-founder of Cellintec L.L.C., which had no role in this research. M.L.S. is an equity holder, scientific co-founder, and advisory board member of Immunitas Therapeutics. The other authors declare no competing or financial interests.Footnotes* This version of the manuscript has improved formatting

Purpose Elimination of the negative component of the unipolar atrial electrogram is a reliable indicator of the creation of a transmural lesion. Contact-force (CF) sensing technology has the potential to increase the durability of pulmonary vein isolation (PVI). In the present multicenter study, we assessed the 2-year sinus rhythm (SR) maintenance rate in patients with paroxysmal atrial fibrillation (PAF) after PVI guided by these two approaches. Methods Two hundred fifteen consecutive PAF patients (62.1 ± 10.1 years, 65 women) were prospectively enrolled. All patients underwent PVI under CARTO guidance according to a systematic contiguous “point-by-point” approach, using radiofrequency energy, and a CF externally irrigated ablation catheter with the goal of at least 10 g (ideally 20 g ) of force. The ablation endpoint of each individual lesion was elimination of the negative component of the unipolar atrial signal. The procedural endpoint was PVI with bidirectional block. Results All PVs were successfully isolated. After 30 min of waiting time, 35 patients (16%) had PV reconnection and in all of them, the PVs were re-isolated. Two years after a single ablation procedure, 187 patients (87%) remained arrhythmia free, without anti-arrhythmic drugs. Of the 28 patients presenting with AF recurrence, 25 had PV reconnection and underwent repeat PVI while in the remaining 3 patients, all four PVs were isolated and extra-PV triggers were identified. There were six groin hematomas and one transient ischemic attack. Conclusions Unipolar atrial signal analysis combined with CF sensing ensures a robust 2-year SR maintenance rate in the treatment of PAF. Clinical trial registration—URL: http://www.clinicaltrials.gov . Unique identifier: NCT02520960.